3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 6. Trans-6-[2-(substituted-1-naphthyl)ethyl(or ethenyl)]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-ones.
A variety of trans-6-[2-(substituted-1-naphthyl)ethyl(or ethenyl)]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-ones were prepared and, upon conversion to their 3,5-dihydroxy carboxylates, were found to have good inhibitory activity against the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the rate-determining enzyme in cholesterogenesis. The most active compounds are 2,4,6- and 2,4,7-trichloro derivatives and would be expected to display about the same potency as the standard compactin upon resolution.
Prugh
J D
JD
Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
Alberts
A W
AW
Deana
A A
AA
Gilfillian
J L
JL
Huff
J W
JW
Smith
R L
RL
Wiggins
J M
JM
D055598:Chemical Phenomena; D002621:Chemistry; D002627:Chemistry, Physical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D066298:In Vitro Techniques; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011714:Pyrans / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009281:Naphthalenes; D011714:Pyrans